DERIVATIVES  OF  PHENYLSTIBINIC  AND  P-ARSANILIC  ACIDS 


BY 

IRVIN  ALVIN  KOTEN 
A.  B.,  North-Western  College,  1920 


THESIS 

Submitted  in  Partial  Fulfillment  of  the  Requirements  for  the 

Degree  of 

MASTER  OF  SCIENCE 
IN  CHEMISTRY 

IN 

THE  GRADUATE  SCHOOL 

OF  THE 

UNIVERSITY  OF  ILLINOIS 


1921 


V S ' 


\0\  %\ 

UNIVERSITY  OF  ILLINOIS 

THE  GRADUATE  SCHOOL 

Jul  y 29 192— 

I HEREBY  RECOMMEND  THAT  THE  THESIS  PREPARED  UNDER  MY 

SUPERVISION  BY IRVINALVIN  K OTEN. 

ENTITLED  DERIVATIVES  OF  PHENYLSTIBINIC  AND  P-ARSANILIC  ACIDS . 


BE  ACCEPTED  AS  FULFILLING  THIS  PART  OF  THE  REQUIREMENTS  FOR 
THE  DEGREE  OF  MASTER  OF  SCIENCE . 


Recommendation  concurred  in* 

Committee 

on 

Final  Examination* 


^Required  for  doctor’s  degree  but  not  for  master’s 


476959 


1 

' . 


■ 


• 

■ . . -.u 


ACKNOWLEDGMENT . 

I wish  to  extend  my  thanks  to  Professor  Roger  Adams  for 
the  interest  shown,  and  for  the  many  suggestions  offered  in  the 
preparation  of  this  thesis. 


Digitized  by  the  Internet  Archive 
in  2016 


https://archive.org/details/derivativesofpheOOkote 


— 1- 

TABLE  OF  CONTENTS. 

Chapter  I . 

PHENYLSTIBINIC  ACID. 

I.  Historical . 3 

II.  Theoretical 3 

1.  Phenylstihinic  Acid 3 

III.  Experimental 9 

1.  Preparation  of  Phenylstihinic  Acid 9 

(a)  The  Sodium  Method 9 

(b)  The  Diazo  Method 11 

2.  Reduction  of  Phenylstihinic  Oxychloride.. 12 

3.  Reduction  of  Phenylstihinic  Acid . 13 

IV . Summary , , , . 

Chapter  II . 

P-ARSANILIC  ACID. 

I.  Historical.  * . 14 

II.  Theoretical 15 

1.  P-Arsanilic  Acid..... 

2.  Atoxyl.  

(a)  Proof  as  to  the  constitution  of  atoxyl is 

III.  Experimental 19 

3 . Atoxyl 19 

2.  Phenylglycine  p-arsenic  acid..... 2 0 

3.  Phenylglycine  p-arsenious  oxide 20 

4.  Phenylglycine-p-arsenious  chloride.  21 

5.  P-amino  phenyl  arsenious  chloride 21 

6.  P-chlor-arsenic  acid 21 

7.  P-amino  phenyl  arsenious  oxide 22 


. 

, . , . . 







. 1 


i : 'I 

...  * * 

. . . , 

........ 

. 

, .....  . 

I .......  j 


8.  Attempts  at  the  preparation  of  Phenylglycine-p-ethyl- 


arsenic  acid.  • * 22 

9.  Attempts  a t the  preparation  of  Di^henyl-p-diarsinic  acid. 

24 

(a)  Cuprous  Chloride  Method 24 

(b)  Ammoniacal  Cuprous  Oxide  Method.  24 

(c)  Copper  Powder  Method.  * 24 

IV . S ummar y . 25 

V . Bibliography 26 


* • • 

...  . 

...  


. 


-3- 

Chapter  I. 

PHENYLSTIBINIC  ACID. 

I.  Historical. 

Twelve  years  after  Bechamp’s  discovery  of  the  first  aro- 
matic arsenical  (1860-63),  Michaelis  began  a systematic  study  of 
the  aromatic  derivatives  of  phosphorus,  arsenic,  and  antimony, 
establishing  first  at  Karlsruhe  and  Aachen  and  then  at  Rostoch  a 
school  of  chemistry  in  this  particular  branch  of  organic  synthesis. 
Michaelis  with  the  aid  of  La  Coste,  Reese,  and  others,  devised 
general  methods  of  preparation  for  the  compounds  of  both  series, 
and  prepared  the  first  aromatic  antimony  derivatives.  The  syn- 
thesis of  aromatic  organo-metalloidal  compounds  has  been  further 
facilitated  by  the  discovery  that  these  compounds  are  obtainable 
through  the  diazo  reaction.  This  process  has  been  applied  to 
aromatic  antiraonates  by  the  Chemische  Fabrik  von  Heyden  of  Dres- 
den . * 

II.  Theoretical. 

The  method  by  which  Michaelis  and  Reese  first  prepared 
aromatic  antimony  compounds  leads  chiefly  to  the  triaryl-stibines . 
More  recently  the  Grignard  reaction  has  been  applied  to  the  pre- 
paration of  aromatic  antimony  derivatives.  Based  on  the  discovery 
made  by  the  Chemische  Fabrik  von  Heyden  that  antimonial  groups 
can  be  introduced  into  the  aromatic  nucleus  through  the  agency  of 
the  diazo  reaction,  certain  aryl-antimony  derivatives  containing 
amino  groups,  such  as  the  antimony  analogues  of  atoxyl,  and 
salvarsan,  have  been  synthesized. 

Several  processes  are  available  for  the  synthesis  of 

aromatic  antimonials.  The  sodium  process  is  available,  but  the 
.(.-Ll.MQr’.g an -Organic  fjuLiprnirifls  nf  /■.  nn^  .Antimony . 


: • 


- • ' * r:  v • 

. 

. , • . - : ! ; - .[ 

• T'.  i r>  ■ ’ * 1 ‘ . ' ' , ':'i 

•>'!•■  ' ■ 1 . ' 

• ’ •>  ‘ ! -i  I • :*  • •:  *r 

- 

•jo:.  $ J J ;rv  ■ r Jr  ; • • . • 

'Jo  • • 

i ■ 


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■ 

• •;  1 

: ' ■ 

V 

. 


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-4- 


reaction  is  considerably  complicated  by  the  greater  tendency  pos- 
sessed by  antimony  of  passing  from  the  triadic  to  the  pentadic 
condition. 

The  following  outlines  show  the  steps  involved  in  two  of  the 
older  methods  for  the  preparation  of  aromatic  antimonials . 

I.  Sodium  Method.1 

CgH^Cl,  SbCl3  and  Sodium. 


(C6H5)3Sn 


(C6H5)2SbCl3 


(C0H5r3SbCl2 


heated 
with  SbCl3 


C0H5SbCl2 

IC12 

C6H5SbCl4 

i Ha0 

C6II5Sb0(0Il)2 


(C6H5)2SbCl 


NaOH 

HC1 


NaOH 

HC1 


(Cf>H5)2Sb0.0H 


(C6H5)3Sb(0H)2 


II.  Grignard  Reaction  For  Aryl  Antimony  Compounds 

C6H5MgBr  and  SbBr3or  SbCl3 

(C6H5)3Sb  and  (CfjH5)3SbX2 
» 

Cl2  | heating  with  SbCl3 

(C6H5)3SbCl2 

(CGH5)3Sb(0H)2 


(C6H5)2SbCl 

(C6H5)2SbCl3 

(C6H5)2Sb0.0H 


C6H5ShCl2 

C6H5SbCl4 


C6H5Sb0(0H)2 

The  modern  improvments  which  have  facilitated  the  pro- 
duction of  aryl -antimony  derivatives  are  two -fold.  First  we  have 
the  application  of  the  Grignard  reaction  to  the  production  of  tri- 
phenylstibine  and  its  homologues.  The  second  improvement  was  the 
discovery  made  by  the  Chemische  Fabrik  von  Ileyden  that  antimony 

(1)  Morgan-Organic  Compounds  of  Arsenic  and  Antimony.  P 294 


■ 


; i 


. :: 


' ■? 


) 


V 


( 


• ' • 

1 ' • ■ ' • ' 

•f  > l 

) 


) 

"7  ■ • 1 ■ ’ 1 ! 

* ’ 

i 1 , 

• - 


-5- 

groups  could  be  introduced  into  the  aromatic  nucleus  through  the 
agency  of  the  diazo  reaction.  This  discovery  first  led  to  the  syn- 
thesis of  antimony  atoxyl . 


NIL 


SbO ( OH ) 2 


by  the 
following 
steps  _ 


NHCOCH3 


NHCOCH3 


IIONO 


SbClo+'NaOH  , x 

NH2  3 SbO (OH) 2 


HOH 


nh2 

SbO (OH) 


0 


The  diazo  process  is  a general  one  and  many  complex  antimony  de- 
rivatives can  thus  be  synthesized. 

1.  PHENYLSTIBINIC  ACID. 

This  acid  was  first  prepared  by  Michael! s and  Reese  by  what 
is  known  as  the  Sodium  Method. 

(CgHg^Sb1  is  first  prepared  by  adding  metallic  sodium  to  a 
mixture  of  SbCl3  and  C3H5CI  in  CgHg.  Besides  (CgHg^Sb  some 
(CgH5)2SbCl3 , (CgIl5)3SbCl2  and  (CgHg^SbO  is  formed  in  the 
reaction. 

SbCl3  + 3C6H5C1  6Na  > (C6H5)3Sb  + 6NaCl 


SbCl3  -t  3C6H5C1  + 4Na 


(C6H5)3sbC12  -h  4NaCl 


The  crude  product  is  purified  by  extracting  the  (CgHg^SbC^ 
with  a solution  of  fuming  IIC1  in  C2HgOH.  By  means  of  chlorine 
(CgHg^Sb  and  (CgHg^SbO  are  converted  into  (CgHg^SbC^  which 
is  obtained  in  thin  needles.  These  are  dissolved  in  ammoniacal 
alcohol  and  by  means  of  II2S,  (CgHg)gSb  separates  at  first  as  a 
crystalline  powder  which  soon  melts  to  form  a colorless  oil.  The 
pure  product  can  then  be  obtained  by  crystallization  from  alcohol 
or  ether. 

Moraophenylchlorstibine2  is  prepared  next  by  heating  together 

(1)  Michaelis  and  Reese,  Annalen  233-234,  P.  43 

(2)  Hasenbaumer,  Berichte  31,  P.  2911-13. 


• ■:••••*'  * . . ' ' r .• 

0 


' 


. 


' ' -i  * ’ • ' 


-r  * 

• . ; ' 1 1 

- 

/ • .'-'.I-  t 

. 

■ . 


. ■ 


■ 


-G- 


in  a tube  (CgHg^Sb,  SbClg  and  some  dry  xylene.  Formerly  the 
desired  result  was  not  obtained  because  the  SbCl3  and  (CgHr^gSb 
were  heated  without  a diluting  agent  which  resulted  in  the  reaction 
being  carried  too  far. 

(CGH5)oSb  + 2SbCl'3  3C3H5SbCl2 

The  black  substance  is  purified  by  first  removing  free 
SbClo  with  HC1  and  then  distilling  in  a stream  of  C02.  At  270-300 
degrees  a thick  fluid  passes  over  which  crystallizes  on  cooling. 

C6H5SbCl2  is  then  converted  into  C6H5SbCl4  by  saturating  it 
ether  solution  with  chlorine.  The  crystals  formed  are  very  hygro- 
scopic, and  with  water  form  CgHgSbO  (OH)^. 

The  crystals  of  C6  \\5  SbCl^  are  dissolved  in  dilute  NaOH  and 
the  filtrate  is  acidified  with  dilute  ITC1  from  which  CgHgSbO (Oil )2 
separates  as  a white  amorphous  powder. 


s 


C6H5SbCl4+  GNaOH  — * CgHgSbO (0Na)2  + 4NaCl  H20  . 

CgHrSbO (0Na)2+  2IIC1  — » CGH5Sb0(0H)2  + 2NaCl. 

The  nrocess  just  described  is  difficult  and  does  not  give 
very  good  yields.  Due  to  the  remarkable  discovery  by  the  Chemischc 
Fabrik  von  Heyden,  that  antimonial  groups  can  be  introduced  into 
the  aromatic  nucleus  through  the  diazo  reaction,  this  acid  is 

o 

prepared  by  a much  more  convenient  method. 

Aniline  is  first  dissolved  in  H2S0_4  and  diazotized  with 
NaN02.  A solution  of  NaOH  is  next  added  to  aqueous  SbClg.  The 
solution  which  is  rapidly  cooled  to  0 degrees  when  a portion  of 
the  sodium  antimonate  separates  is  then  treated  with  the  diazonium 
solution.  The  evolution  of  nitrogen  is  favorably  influenced  by 
(3)  Friedlander  1912-14,  P.  1084  -D.R.P.  254,421. 


• ' 


' • ■ ; . ” • 

I-  't  i.  1 ) . 

* ; ' • 

■ 

• ■ j • 

. . . . 


-7- 


The  addition  beforehand  of  copper  paste  or  CUSO4.  After  several 
hours  the  excess  of  NaOH  is  almost  neutralized  with  dilute  II2SO4 
and  CgHgSbO^H^  is  precipitated  from  the  filtrate  by  means  of 
dilute  HC1.  The  crude  product  is  purified  from  any  Sb203  by  dis- 
solving it  in  hot  concentrated  HC1  and  saturating  the  solution 
with  NH4CI.  The  NH4CI  increases  the  chlorine  ion  concentration 
and  thus  aids  in  converting  the  Sb202  into  SbC^.  Upon  cooling 
C0H5SbO(OCl)2  separates  in  leaflets  and  is  dissolved  in  aqueous 
NagCC^.  The  purified  CgH5Sb0(0H)2  is  then  precipitated  by  adding 
HC1  to  the  alkaline  filtrate. 


NH2 

Q'+  HgS04 


> 


NH2'H2S0 


a 


4 


NH2H2SO4 


0 


HONO 


N2HSO4 


+ 2II20 


SbCl3  + 5N aOII  > Na2HSb03  -t  3NaCl  + 2H20 


n2hso4 

0 + Na2HSb03  + 2NaOH 


Sb03Nao 

Q + Na2S04  + 2H20 


3b03Na2 

0 f h2so4 


SbO (OH ) 2 

Q)  + Na2S04 


SbO (OH) 


+ HC1 


SK-Cl 


O' 


Cl  + 4NaOH 


„ * 0 

Sb-ONa  ^ 

PjNONa  + 2HC1 


8b -0 

^C1 

Cl  + 2H20 


0 

ON  a 


Sb 


\ 


ONa  -h  2NaCl  -f  2H20 


Sb  - OH 

N01-I  + 2NaCl 


t •{ 


-8- 


Phenylstibinic  acid  was  fitst  described  by  Hasenbaumer , a 
pupil  of  Michaelis.  It  is  a white  amorphous  powder  difficultly  sol- 
uble in  water,  but  quite  soluble  in  NH4OH,  NagCOg,  dilute  NaOH 
and  hot  concentrated  IIC1.  In  the  moist  state  it  has  a faint  but 
not  unpleasant  odor.  It  remains  unchanged  at  285  degrees.  Heated 
on  a platinum  foil  it  darkens  and  burns  with  a bright  flame. 

The  formula  according  to  Hasenbaumer  is  CgHgSbOgHg.  Schmidt 
however  in  1920  observed  that  it  took  less  than  one  mole  of  alkali 
to  dissolve  the  acid,  and  that  the  solution  of  the  acid,  in  the 
meagre  amount  of  alkali,  consumed  more  of  the  alkali  (shown  by 
phenolphthalein)  until  an  end  point  was  reached.'  He  concluded 
therefore  that  phenylstibinic  acid  is  in  a polymerized  form  which 
breaks  up  into  a monomolecular  form  when  dissolved  in  alkali.  On 
acidifying  it  again  assumes  its  polymerized  form. 

According  to  Schmidt  the  first  neutralization  occured  with 
a ratio  of  one  of  sodium  to  three  of  antimony.  It  has  therefore  a 
trimolecular  formula. 

Structurally  it  would  appear  to  be- 
OH  ,0H 

C,H,Sb  = 0 C H Sb=  0 

6 * '0  <•  * '0 

C H Sb^  0 or  C,  H-  Sb'Coj; 

fr  5 "0  * * V 

C H Sb7-  0 C.H  Sb^O 

^ b V0H  ^ 5 X0H 

^0 

The  monomolecular  formula  would  be  C.  H Sb-OH.  It  was  act- 

s N0H 

ually  shown  by  analysis  that  the  acid  exists  in  a polymerized  form. 

If  phenylstibinic  acid  is  repeatedly  washed  with  water^  a 

turbid  filtrate  results.  This  is  due  to  its  assuming  a colloidal 

form.  That  it  assumes  such  a form  is  also  indicated  by  the  fact 

That  it  is  soluble  in  solvents  used  for  the  solution  of  high 
(1)  Schmidt  Annalen  1920,  421,  P.  174 


■ 

' 

:• 

■ ■ 

■ ' ' D 

. 


. 

. 


-9- 


molecular  cellulose  esters.  Its  weight  also  changes  with  varia- 
tions in  atmospheric  pressure,  temperature,  and  humidity. 

The  sodium  salt  of  C0H5SbO(OH)2  has  "been  prepared  by  dis- 
solving 2.5  grams  of  the  acid  in  25  cc . water  and  10  cc • N-NaOH. 

The  alkali  salt  is  then  precipitated  from  the  filtrate  by  20fo  NaOH. 
These  salts  are  suitable  for  therapeutic  injections . 

When  m-NOoCgH^SbO (0H)2  is  reduced  with  zinc  and  NH^Cl  in 
an  alcohol  solution  the  amino  compound  is  fifcst  formed.  Further 


reduction  gives  the  stibinoxy  compound 
Sb-OH 


rV°H 

LJno2 


^0 
Sb-OH 


X0H 

IH2 


Sb-0 
NH2 


-i-  2K20 


It  has  been  found  that  SnCl2  will  reduce  C0H5SbO(OH)2  to 


C^HgSb=0,  while  NaHSOg  will  reduce  the  acid  to  < VSh=Sh<  > 


Sb=0 

o - 


(c6HR)2sb2o 


(c6H5)3s,b 


C6H5Sb=Cr,II5 
ITI.  Exnerimental . 

1.  Preparation  of  Phenyls tibinic  Acid. 

(a)  The  Sodium  Method. 

The  preparation  of  ^he  older  sodium  method 

v/ as  tried.  (C^H^gSb  was  prepared  first.  50  grams  of  metallic 

sodium  were  powdered  by  the  usual  method  of  heating  one -half  inch 
dubes  ©f  Na  in  xylene  until  the  xylene  begins  to  boil  and  then  to 
pulverize  the  cubes  by  means  of  a stirrer.  The  apparatus  was 
fitted  with  a mercury  seal  After  the  sodium  had  been  powdered, 
the  xylene  was  decanted  and  the  sodium  washed  with  benzene.  Then 
100  cc.  of  benzene  were  added.  36.4  grams  of  SbClg  were  dissolved 
in  benzene  and  added  through  the  reflux  condenser.  49  cc.  of 


. 


. 


' 1 ' ' ■■  ■•.■  , V 0.1  . 


•'  ' ' i <r  o 


-10- 

freshly  distilled  C^H^Cl  were  then  added  and  also  the  remainder  of 
600  cc.  of  CgHg.  The  mixture  was  stirred  for  twenty-four  hours. 
The  reaction  was  very  slow  in  starting.  It  was  never  violent,  hut 
warmed  up  gradually. 

After  24  hours  the  solution  was  filtered  with  difficulty. 
Suction  could  not  he  used  because  of  the  evaporation  of  C qII ^ . The 
filter  was  of  a dark  hrown  color  when  moist  and  grey  when  dry.  It 
had  a nauseating  odor.  The  filtrate  was  of  a yellow-orange  color 
and  had  an  agreeable  odor.  Almost  500  cc . filtrate  was  obtained, 
from  which  was  then  distilled.  Quite  a large  excess  of  metal- 

lic sodium  was  present  in  the  filter. 

About  100  cc.  of  the  residual  filtrate  was  allowed  to  cry- 
stallize in  a dish.  No  crystals  formdd.  Only  a viscous  syrupy 
yellow-brown  liquid  remained.  CgHg  was  added  and  the  solution 
cooled  on  ice.  Small  white  crystals  now  separated.  Fuming  HC1 
and  some  alcohol  was  then  added  to  the  mixture  and  warmed  on  the 
steam  bath.  The  alcohol  dissolved  the  (CgHg^SbClg , and  was  then 
decanted  from  the  remaining  yellow  oil.  This  oil  was  then  placed 
in  a flask  and  chlorine  passed  over  its  surface.  A yellow  amor- 
phous precipitate  formed.  It  was  dissolved  in  boiling  alcohol  and 
allowed  to  cool.  Yellow  needle-like  crystals  formed.  After  re- 
crystallization and  decolonization  they  were  white.  These  cry- 
stals dissolved  easily  in  a mixture  of  NH^OH  and  alcohol.  IlgS  was 
passed  into  this  solution  for  an  hour.  Only  a very  small  white 
precipitate  formed. 

On  account  of  poor  yields,  this  method  was  abandoned  for 
the  much  more  convenient  diazo  method. 


‘ •'  -r 

. 

i >n  r, 

t 

. 

■ 

. 

■ 

I'  Y 

. . ; ■ j 


-11- 


(b)  The  Diazc  Method. 

1 gram  mole  of  CgH^NHg  was  dissolved  in  one  liter  of  water 
containing  1.5  gramemoles  of  H2SO4  and  diazotized  with  a solution 
of  1 mole  NaNOg.  The  temperature  was  kept  between  4 and  7 degrees. 
A solution  of  600  grams  NaOH  in  3 liters  of  water  was  added  to 
aqueous  SbClg  prepared  by  dissolving  (0.5  mol.)  of  Sbo03  in  764 
grams  of  HC1  (sp.  gr.  1*123) . The  solution  which  was  rapidly 
cooled  to  0 degrees  when  a portion  of  the  NagHSbOg  separated  was 
then  added  slowly  to  the  diazo  solution  with  vigorous  stirring.  A 
yellow-brown  foam  formed  very  rapidly.  Copper  paste  was  then 
added  to  hasten  the  evolution  of  nitrogen.  It  was  found  that  a 
solution  of  CuSO^  worked  as  well  as  copper  paste.  The  solution 
was  now  stirred  for  three  hours.  At  the  end  of  that  time  it  was  of 
a brown  color.  The  excess  NaOH  was  then  neutralized  with  dilute 
HgSO^,  and  the  mixture  filtered.  The  filtrate  was  of  a clear 
orange  color.  The  filter  was  brown  and  pasty  like. 

When  IIC1  was  added  to  the  filtrate  a white-orange  precipi- 
tate formed.  This  was  allowed  to  stand  for  twelve  hours.  Fil- 
tration was  difficult  due  to  the  pasty  wax-like  precipitate. 

The  crude  product  was  purified  from  Sb^Og  by  dissolving  it 
in  600  cc.  dilute  HC1  and  heating  to  boiling.  While  hot  the  sol- 
ution was  saturated  with  dry  NH^Cl  and  allowed  to  cool.  Red  leaf- 
lets of  phenylstibinic  oxychloride  separated. 

The  phenylstibinic  oxychloride  was  dissolved  in  dilute 
aqueous  NagCOg  which  gave  a red  solution.  This  solution  was  then 
acidified  with  HC1.  A white  precipitate  formed.  After  reprecipi- 
tation a white  amorphous  powder  was  obtained.  It  had  a very  irrit- 
ating action  on  the  mucuous  membrane  of  the  nose.  The  yield  was 


' 

. 

. 

’ 


. 


. • 


. 


-12- 


100  grams 


2.  Reduction  of  Phenylstibinic  Oxychloride 


It  was  attempted  to  reduce  phenyl stilbinic  oxychloride  hy 


means  of  nascent  hydrogen  to 


and  then  to  form  a condensa- 


tion product  "between  the  stibine  and 


& three  liter  flask  was  set  up  for  the  reduction.  Passing 
through  the  stopper  in  the  flask  was  also  a dropping  funnel  and 
a glass  tube,  which  was  used  to  draw  off  the  ether  layer.  A small 
mercury  seal  was  fitted  to  the  top  of  the  condenser.  All  stoppers 
were  always  coated  with  wax  to  prevent  air  from  leaking  into  the 
apparatus . 

Fifty  grams  of  phenylstibinic  oxychloride,  made  by  dissolv- 
ing phenylstibinic  acid  in  hot  concentrated  IIC1,  and  allowing  the 
solution  to  cool,  when  the  oxychloride  would  separate,  were  mix- 
ed with  300  grams  of  amalgamated  zinc  dust,  and  placed  in  the 
flask.  Enough  ether  was  then  added  to  cover  the  mixture  to  the 
extent  of  one  half  of  an  inch.  Concentrated  HC1  was  then  allowed 
to  drop  into  the  flask  at  the  rate  of  about  ten  drops  j)er  minute. 
The  reaction  was  allowed  to  proceed  for  three  days.  At  the  end  of 
that  time  the  ether  layer  which  had  a browniHh  tinge  was  forced  up 
into  a separatory  funnel  by  means  of  water  poured  in  at  the  top  of 
the  condenser.  The  ether  solution  became  a turbid  yellow.  During 
this  time  air  was  kept  away  from  the  ether  by  means  of  a stream  of 
COg  passed  over  its  surface*  The  ether  solution  was  then  dis- 
tilled under  diminished  pressure  in  the  presence  of  COg*  No  dis- 
tillate was  obtained  in  the  receiver.  Instead  a viscous  yellow- 
brown  residue  remained  in  the  distilling  flask,  which  turned 
black  on  standing.  Within  a few  days,  on  exposure  to  the  air,  the 


i ' l : ' 

. 


K > 

■ 

' 

' • : . [ ] i oi 

■-in'  ; '•  >*t'  . • • ' 

■ • • , 


-13- 


black  color  turned  to  a yellow-white,  and  seemed  to  disappear  some 
what.  The  residue  was  insoluble  in  ether,  but  when  a few  drops 
of  HC1  were  added  it  dissolved  readily.  Because  the  residue  was 
so  small  and  gummy  nothing  was  done  to  identify  it. 

Another  reduction  of  the  same  amount  as  the  preceeding  was 
again  made.  The  ether  solution  this  time  was  drawn  directly  into 
freshly  distilled  C^H^CHO.  No  visible  reaction  took  place. 

Concluding  that  possibly  the  reduction  was  not  continued 
for  a long  enough  period  of  time  the  reaction  was  repeated  and 
allowed  to  proceed  for  four  days.  Distillation  of  the  ether  layer 
however  gave  no  results. 

It  was  now  thought  that  a change  of  solvents  might  be  tried 
and  accordingly  CHgOK  was  used  in  place  of  ether.  The  CHgOPI  mix- 
ture was  then  subjected  to  steam  distillation  in  the  presence  of 
COg*  The  distillate  contained  no  reduction  products. 

Dilute  CIIgCOOH  was  now  used  in  place  of  concentrated  HC1, 
and  the  reaction  allowed  to  proceed  for  three  days.  The  reaction 
mixture  turned  black  and  spongy,  nearly  filling  the  entire  flask. 
NaOH  was  then  added  to  neutralize  the  excess  CH^COOH.  No  results 
were  obtained.  The  residue  was  refluxed  with  equal  parts  of  C2H5OI 
and  C^IIq.  Copper  powder  was  added  as  a catalyst.  After  the  sol- 
vents were  distilled  off,  a yellow-brown  residue  remained.  When 
dry  it  had  a peculiar  pungent  odor  and  was  stable  in  air.  It  had 
no  definite  melting  paint.  It  was  soluble  in  HCl  and  was  precip- 
itated by  NaOH,  in  which  it  was  soluble  in  excess.  It  had  pro- 
perties which  resembled  those  of  Cgll^SbO (0H)2* 

3.  Reduction  of  Phenylstibinic  Acid. 

Since  no  definite  positive  results  could  be  obtained  with 


. 

I ■ • * 

'I  ( 


■ ■ 


•f 

. 1 ' 1 liiTf 


■ ‘ 


r 1 

• ' 


' • 

• 

. 

* 

.. 

. ' ■’")•?  r.  ’ i ■ 

' ■ ' 0 ' 


-14- 

phenyl  stibinic  oxychloride,  phenylstibinic  acid  w as  used  in  the 
reductions.  Ether  and  dilute  HC1  were  now  used.  During  the  re- 
action the  ether  solution  became  yellow,  and  was  stable  in  air. 
Unon  evaporating  the  ether  solution,  in  a vacuum,  very  small 
needle-like  crystals  separated.  These  crystals  however  were  not 
very  stable  in  air  and  on  attempted  filtration  and  purification 
a gummy  mass  was  obtained.  The  experiment  was  repeated  with  the 
same  results. 

A change  in  the  kind  of  reducing  agent  was  now  made . Ten 
grams  of  aluminium  powder  were  added  to  a solution  of  25  grams  of 
CgHrjSbC^OH^  in  NaoCOo.  Hydrogen  was  evolved  very  readily.  The 
ether  solution  became  slightly  yellow.  After  three  days  the  ether 
layer  was  separated,  but  was  found  to  be  stable  and  to  contain  no 
CgHsSbHg.  No  further  attempts  at  reduction  were  made. 

V . Summary . 

*0 

1.  Cf^Sb-oiI  can  be  obtained  very  readily  and  in  good 


OH 


yields  by  means  of  the  diazo  reaction. 

2.  Attempts  at  the  reduction  of  C0ll5SbO(OCl)2  and  C(jH5Sb0(0H|[)2 
in  an  effort  to  obtain  C0H5SbH2  failed. 

3.  Since  CgHgSbC^OH^  has  been  proved  to  exist  in  a poly- 
merized form  in  acid  solution,  this^it  is  concluded^raay  be  the 
cause  of  the  inability  to  obtain  CgllgSbl^  by  the  reduction  of 
CgHgSb0(0H)2  in  acid  solution. 

Chapter  II. 

P-Arsanilic  Acid. 

I.  Historical. 

To  Be'champ  belongs  the  honor  of  having  prepared  the  fifcst 
aromatic  arsenical  compound.  This  work  was  done  between  the  years 


- 

. 

* 

- 

, ; 


. : * 


. 0 


1860-63.  BeXchamp 1 s compound  which  was  supposed  to  have  been  an 
anilide  of  arsenic  acid  was  tried  in  therapeutics  in  or  about  the 
year  1902.  Thomas  and  Breine  employed  the  compound  in  the  treat- 
ment of  sleeping  sickness.  Because  of  the  comparatively  non- 
toxic nature  of  the  drug  it  was  named  atoxyl . It  nroved  to  be  so 
satisfactory  that  Ehrlich  and  BeTtheim  undertook  a systematic 
investigation  with  the  result  that  atoxyl  was  proved  to  be  the 
sodium  salt  of  arsanilic  acid.  Researches  were  now  started  in 
special  laboratories,  notably  those  at  the  Georg  Speyer  Hospital 
in  Frankfort  and  at  the  Hochst  FarBwerke  vormals  ^eister  Lucius 
und  Briinning.  In  England  the  chemists  of  Messrs  Burroughs 
Wellcome  & Co,  have  carried  through  a considerable  amount  of  re- 
search on  atoxyl  and  its  derivatives.  And  in  America,  especially 
since  the  World  War,  greater  interest  than  ever  before  has  been 
shown  in  arsenical  preparations.  A few  of  these  will  be  discuss- 
ed in  this  paper. 

II.  Theoretical. 

1.  P-Arsanilic  Acid. 

The  compound  obtained  by  BeXchamp  during  the  years  1830-63 
was  a colorless  condensation  product  obtained  from  the  reaction  of 
aniline  and  arsenic  acid.  He  noticed  that  the  compound  reacted  as 
a monobasic  acid,  giving  rise  to  metallic  salts  of  definite  char- 
acter, and  was  not  hydrolyzed  by  means  of  aqueous  caustic  potash. 
Because  of  its  acid  pr*  operties  he  concluded  that  it  was  an  anilide 
and  accordingly  named  it  " Phenarsenyl -ammonium” . The  formula 
assigned  to  it  was  [(^igHsHgAsO^N]  0 .HO , according  to  the  old 
notation. 

The  third  period  in  the  history  of  organic  arsenic  and 


. 


■ 


-16- 

antirnony  compounds  comnenced  in  1907  when  Ehrlich  and  Belthei-rn, 

demonstrated  the  true  constitution  of  atoxyl*  These  two  men  shov/ec 

that  the  action  of  arsenic  acid  on  aniline  is  comparable  to  the 

action  of  sulphuric  acid  on  the  same  base.  In  both  cases  the 

NH2 

acidic  group  enters  the  aromatic  nucleus  giving  rise  to  Q 

NHo  SOgOH 

and  On  respectively.  The  former  is  termed  sulphanilic 

X y>  U 

As - OH 

acid  OH  an<^  accordingly  the  latter  arsanilic  acid. 

P-arsanilic  acid  can  be  prepared  by  slowly  heating  to  170- 
200  degrees  for  two  hours,  in  a vessel  fitted  with  a stirrer,  188 


grams  of 


qK2  mixed  with  140  grains  of  arsenic  acid.1 


The 


product  is  then  mixed  with  water,  made  alkaline,  and  the  excess 
base  distilled  off  with  steam.  The  residue  is  then  cooled,  fil- 
tered, concentrated,  and  neutralized  with  IIC1,  when  crude  arsenj 
ic  acid  separates.  This  product  is  then  dissolved  in  aqueous  NaOH 
The  solution  which  should  be  only  faintly  alkaline  is  boiled  with 
animal  charcoal  and  filtered  into  alcohol,  when  the  sodium  salt 
(atoxyl)  separates  in  a crystalline  form.  The  by-product  di-4- 
amino  diphenylarsenic  acid  remains  dissolved,  as  its  sodium  salt 
is  soluble  in  alcohol.  The  free  p-arsanilic  acid  is  liberated 
from  atoxyl  by  the  addition  of  dilute  IIC1. 

The  acid  is  sparingly  soluble  in  water  or  CgHgOH,  more  so 
in  CH3OH,  and  insoluble  in  (0285)20,  C^Hg  or  CIICI3.  It  is 
appreciably  amphoteric  dissolving  in  excess  mineral  acid  from 
which  it  can  be  precipitated  by  1^028302*  It  can  be  recrystallia- 
ed  from  alcohol  and  water  with  two  molecules  of  water  of  cry- 
stallization. 

2.  Atoxyl*  Atoxyl  the  sodium  salt  of  p-arsanilic  acid,  as 
(1)  Morgan.  Organic  compounds  of  Arsenic  and  Sb.  P158 


/Ai 

' 

' 

- 

. 


. 

' »-( 

■ 

. 


-17- 


has  been  stated  beforehand  derives  its  name  from  the  fact  that  it 
is  comparatively  non-toxic.  It  has  been  given  various  synonyms 

c 

such  as  Arsamin,  Soamin,  Natrium  Ars an ilium. 

The  water  content  of  atoxyl  is  variable.  Ehrlich  and 
Eeitheilh  state  that  it  is  obtainable  with  two  and  six  molecules 
of  water  of  crystallization,  according  to  the  solvent  used  in 
crystallization  of  the  comrjound.  The  more  hydrated  forms  lose 
water  by  eff lorvesence . Commercial  specimens  contain  from  three 
to  five  and  one  half  moles  of  water.  The  product  introduced  by 
Qurroughs  Wellcome  & Co.,  under  the  name  of  Soamin,  is  in  the 
form  of  well-defined  colorless  crystals  containing  five  moles  of 
water.  Dr.  Mart indale ' s preparation  contains  approximately  three 
moles  of  water. 

As  soon  as  the  therapeutical  value  of  atoxyl  was  discovered 

several  thought  it  impossible  to  sterilize  an  aqueous  solution  of 

the  salt  at  100  degrees,  as  a part  of  the  substance  would  decom- 
1 

pose . 

Ehrlich  and  Beitheirn  however  claimed  atoxyl  to  be  stable. 
It  was  shown  however  by  Schmitz  that  the  aqueous  solution  of  sod- 
ium-arsanilate  and  other  salts  of  arsanilic  acid  split  out  ars- 
enic acid  from  the  molecule.  This  was  determined  quantitatively. 

A solution  of  atoxyl  was  heated  for  an  hour  in  a Koschsher  Ster- 
ilizer, then  for  a half  hour  in  an  autoclave  and  then  at  various 
temperatures.  After  cooling,  IICl  was  added  to  precipitate  ars- 
enic acid.  The  product  remaining  in  solution  was  converted  into 
the  Resorscin-azo  dye.  The  filtrate  was  decolorized  with  animal 
charcoal  and  the  remaining  arsenic  acid  was  precipitated  as  mag- 
(l)  Schmitz  Ber.  1914,  47,  363. 


' 

' 

• 't  I 

• . • 


-18- 


nesium  ammonium  arsenate. 

The  adherence  of  arssinic  groups  to  the  aromatic  nucleus 
has  been  studied  by  E.  Schnitz  who  heated  atoxyl  with  various  pro- 
portions of  aqueous  alkali  at  100  and  130  degrees.  The  maximum 
decomposition  was  obtained  by  heating  solutions  containing  one  mole 
of  p-arsanilic  acid  with<x8  moles  of  NaOH.  The  instability  dimin- 
ished when  more  alkali  was  added.  The  salt  is  most  stable  in  the 
presence  of  an  extra  half  molecule  of  NaOH.  Y7ith  this  extra  one- 
half  molecule  there  is  no  hydrolysis. 

The  instability  of  atoxyl  was  traced  to  some  interaction 
between  the  amino  group  and  the  second  -OH  of  the  arsenic  complex. 

Other  alkali  such  as  lithia  and  even  carbamide  behave  sim- 
ilarly. 

The  stabilizing  effect  of  excess  alkali  is  due  to  the  sat- 
uration by  the  NaOH  of  the  second  -OH  radical. 

The  acyl  derivatives  of  atoxyl  are  more  stable  as  the  com- 
bining power  of  the  amino  group  is  diminished  by  acylation. 

The  structural  formula  assigned  to  arsanilic  acid  by 
, Nil- As  ^qi  i 

Beahamp  was  Q . One  mole  of  NaOH  was  required  to  neu- 

tralize one  mole  of  the  acid.  Fourneau  gave  the  formula  for  atoxyl 
NH-As-nvo  o Hor 

as  /N  \q^j  Ehrlich  and  B^T.theim.  however  give  the 

^ As'!vi  ci) 

formula  for  atoxyl  as  Q 

NH2 

(a)  Proof  as  to  the  Constitution  of  Atoxyl. 

The  constitution  of  p-arsanilic  acid  has  been  demonstrated 
by  various  methods . 

1.  Atoxyl,  its  sodium  salt  is  not  an  anilide.  Its  aqueous 
solution  can  be  heated  with  alkali,  concentrated  HC1,  3n$  HgSO^ 
(l)  Bertheim  and  Ehrlich  Ber.  1907,  40,  3292. 


■ 


. : ' 

■ 


r.  ' r ! if  • 


: v,  > «r.« 


. 


-19- 


to  boiling  without  the  splitting  out  of  aniline.  This  is  only 
possible  by  heating  under  pressure  above  its  boiling  point  or  by 
fusion  with  caustic  alkali.  -Since  anilides  are  easily  hydrolyzed 
and  atoxyl  is  not,  the  arsenic  group  is  therefore  firmly  attached 
to  the  nucleus. 

2.  Atoxyl  has  a primary  amine  group  and  shows  all  the  re- 
actions as  such.  It  can  be  diazotized  and  its  diazo  solution  can 
be  combined  with  amines  and  phenols  to  give  dyestuffs.  It  can 
also  be  acetjrlated. 

3.  P-arsanilic  acid  is  an  aromatic  acid.  In  ammoniacal 
solution  it  gives  a calcium  and  magnesium  salt  at  the  boiling 
point.  In  the  cold  no  salts  of  calcium  and  magnesium  are  formed. 

It  is  easily  converted  into  ^ ^ by  HI. 

I 

4.  The  -NHo  group  is  in  the  para  position,  because 
kP  can  be  obtained  as  shown  in  (3). 


III.  Experimental 
1.  Atoxyl. 


^0 

As  ~0H 
Q x0Na 

NHo 


This  compound  was  prepared  by  dissolving  45  grams  of  0 


//0 

As -Oil 
OH 


NH. 


in  10  grams  of  NaOH  dissolved  in  80  cc.  water.  The  solution 
was  warmed  and  allowed  to  cool.  Atoxyl  crystallized  in  clusters  of 
long  slender  needles.  The  yield  was  49  grams.  The  crystals  were 
insoluble  in  CgH^OH  but  easily  soluble  in  water.  On  the  addition 
of  a few  drops  of  HC1  to  an  aqueous  solution  of  the  salt  a white 

As*8h 

crystalline  precipitate  of  Q xoiI  was  obtained.  The  mother 
liquor  from  the  cry-  stallization  of  atoxyl  was 

allowed  to  stand  for  twelve  hours.  Large  crystals  with  very  defin- 
ite angles  separated.  They  were  very  eff lorvescent . When  exposed 


. 


. 


-20- 


to  the  air  for  about  five  minutes  they  became  opaque,  but  kept 
their  shape  for  an  indefinite  time.  The  water  of  crystallization 


was  determined  and  found  to  be  five  moles  of  water. 


A ^/0 

As 'OH 

X0H 


108  grams  of 


OH 


0 


2.  Phenylglycine  P-Arsinic  Acid. 

0 NH  CH2C00H 

ONa  were  dissolved  in  320  cc. 

nh2 

of  water  and  warmed  gently.  Then  a solution  of  64  grams  of 


C1CII2C00H  in  80  cc . of  water  was  added.  The  mixture  was  heated 
in  a reflux  apparatus  for  6-8  hours.  It  was  found  that  heating 
for  seven  hours  with  a low  flame  gave  the  best  results.  It  was 


also  found  that  it  was  necessary  to  use  atoxyl  in  the  preparation 

As  -qj  i 

of  this  acid  instead  of  using  Q '''oh  with  a calculated  amount 

NH2 

of  NaOII. 

After  refluxing  for  seven  hours  the  mixture  was  cooled  in 
ice.  A color  change  was  now  noticed  in  the  solution  as  it  cooled. 
When  hot  it  was  pink  and  green  when  cold.  On  cooling  for  some 
time  very  minute  crystals  separated.  These  were  filtered  off  and 
recrystallized  from  hot  water.  A 69$  yield  was  obtained. 

The  acid  was  easily  soluble  in  hot  water  and  in  concentrated 
HC1,  but  only  sparingly  soluble  in  dilute  IIC1.  It  was  also 
easily  soluble  in  alkali  hydroxides  carbonates  and  acetates.  It 
did  not  melt  at  295  degrees.  The  glycine  group  is  firmly  attached 
and  resists  hydrolytic  action.  \S-G 


0 
NII.CHgCOOH 


3.  Phenylglycine-p-arsenious  oxide. 

As  oh 

69.5  grams  of  oil  were  dissolved  in  1150  cc . 

NH  CH2C0GH 

water  and  160  cc.  2-N  NaOII  and  16  grams  of  El  and  416  cc.  dilute 
II2SO4  (1-5)  were  added.  Sulphur  dioxide  was  then  passed  into  the 
solution  for  six  hours.  The  temperature  was  never  allowed  to  ex- 
ceed 20  degrees.  At  the  end  of  that  time  cold  concentrated  NH4OH 


' •’  '1  i > 

■ ■ ] > 

•I  • > 


■ \ 


■ . n ^ ■ ')  • . '>  •;  • • < ' at 

■ • J . • 

. -:if  I - •<  : : f ’ 

. ; i • • S if  t-:  J • 7 " • 1 ' ■ ' ' V ' M ; \ P * 


...  ••  ; '•  » 7 ;•  ; • • 


j;  r> 


. 


•• 


. 


. 


. 


* 


. o .« • ■;  1 ; - *i  ■ 

. ’ 2»n 


-21- 


was  added  drop  by  drop.  As  the  heat  of  reaction  was  so  great  ice 
was  added  to  keep  the  temperature  below  10  degrees.  NH4OH  was 
added  until  the  solution  was  strongly  alkaline.  The  solution  was 
then  filtered  and  dilute  HgSO^  (1-5)  was  added  as  long  as  a pre- 
cipitate formed.  The  product  was  curdy  and  yellow,  which  on  dry- 
ing became  very  hard  and  brittle.  It  was  quite  soluble  in  alkali. 
Due  to  the  low  yields  of  this  compound  no  further  experimental  work 
was  don*3  3 + - 


KI  in  water  were  added  and  SO2  passed  into  the  solution  which  was 
cooled  by  a mixture  of  salt  and  ice.  A white  flaky  precipitate 
formed,  which  was  hastened  by  the  addition  of  CH3COOH.  The  sol- 
ution was  then  aerated  to  remove  excess  S02»  It  was  then  filtered 
and  the  precipitate  washed  with  CH3COOH  and  finally  with  absolute 
(€21*5)20.  The  compound  melted  at  120  degrees.  It  was  very  sol- 
uble in  water  and  NaOH  with  which  it  formed  the  sodium  salt 


as  those  given  for  Phenyl  Glycine  P-Arsenious  Chloride  were  fol- 
lowed. CH3COOH  was  not  added  however  as  the  compound  separated 
within  two  minuted  after  SO2  had  been  bubbled  through  the  solution. 
The  compound  melted  at  138  degrees,  and  was  soluble  in  H2O, 

CH3OH  and  C2H50H. 


in  concentrated  IIC1  in  which  the  latter  is  very 


NH -CH2C0CH 


soluble.  A few  drops  of  a concentrated  solution  of 


NH-CI^COONa 


5.  P-Amino  Arsenious  Chloride  (J) 

NH2«HC1 

In  the  preparation  of  this  compound,  the  same  directions 


6.  P-Chlor-Arsinic  Acid 


Cl 


. 

• i 


-22- 


As -OH 


This  compound  was  prepared  by  dissolving  30  grams  of  Q N0H 

NHo 

in  45  grams  of  concentrated  H2SO4  and  60  cc.  HgO.  The  sol-  ^ 

ution  was  then  diazotized  with  15.3  grams  of  NaNOg.  A cold  sol- 
ution of  21.6  grams  of  CugClg  in  100  cc.  concentrated  IIC1  was 
then  added.  After  the  solution  became  green  a very  finely  divided 
precipitated  formed.  This  precipitate  was  soluble  in  warm  alcohol, 
insoluble  in  cold  but  soluble  in  hot  HgO.  It  was  therefore  recry- 
stallized from  hot  water  containing  a little  alcohol.  An  cooling 
minute  crystals  formed.  They  had  a buff  color,  which  could  not 
be  removed  with  bone-black  The  crystals  did  not  melt,  but  de- 
composed at  a high  temperature. 

The  compound  was  analyzed  for  arsenic  by  the  method  of 

Robertson.^  Calculated-31 . 69^  As.  Found-31 .48^. 

As=0 

7.  P- Amino  Arsenious  Oxide.  Q 

NH2 

In  the  preparation  of  this  compound,  directions  similar  to 

As=0 

those  given  for  the  preparation  of  Q were  followed. 

Nil  ‘CHpCOOH 

A white  precipitate  formed  which  after  it  Had  been  filtered  and 
exposed  to  the  air  beeame  slightly  yellow  in  color.  The  crude 
product  was  purified  by  dissolving  27  grams  in  220  cc.  water  and 
180  cc.  2N-NaOII.  It  was  shaken  with  ether.  The  water  layer  was 
filtered  off  and  mixed  with  108  cc.  9N-NH/J.C1  when  the  compound 
precipitated. 

The  compound  was  soluble  in  acetone,  alcohol,  dilute 
acids  and  NaOII  and  not  very  soluble  in  (Cgt^jO  and  CHClg. 

8.  Attempts  at  the  Preparation  of  Phenylglycine-P-Ethyl 

AS^QTI 

Arsinic  Acid.  CgH, 


16.8  grams  of  Q 


As-C1  NH  • CHoCOOII 


•Cl 


were  dissolved  in  80  cc.  of 


NH  • CHoCOOII 

(1)  Robertson,  J.A.C.S.  P.&82 


- 


. 


. 


-23- 


CpHr)OH.  This  solution  was  then  added  slowly  to  an  ice  cold  sol- 
ution of  20  cc.  lON-NaOH.  The  solution  was  kept  cold  to  avoid  de- 

AsCC1 

composition  of  the  Q while  being  added  to  the  NaOH  sol- 

Yh«ch2cooh 

ution.  The  solution  was  then  filtered  from  precipitated  NaCl.  8 
cc  . of  CrjH^I  decolorized  by  shaking  with  mercury  were  added.  No 
heat  of  reaction  was  noticed.  The  solutionwas  allowed  to  stand 
for  twelve  hours.  It  was  then  diluted  with  300  cc . water  and  the 
resulting  turbidity  removed  by  shaking  with  ether  and  separating 
the  aqueous  layer.  While  stirring  freshly  precipitated  AgCl,  ob- 
tained from  25  grams  of  AgNOg,  was  added  to  remove  free  iodine 
from  the  solution.  The  Agl  was  filtered  off,  and  the  solution 
accidified  with  concentrated  HC1  until  it  reacted  with  congo  paper. 
It  was  then  concentrated  on  a steam  bath.  NaCl  separated.  On 
evaporating  to  dryness  a black  tarry  residue  remained,  which  was 
soluble  in  alcohol  and  insoluble  in  ether.  As  yet  it  has  not  been 
found  whether  this  resinous  material  contains  some  of  the  expected 
product . 

Instead  of  CgH^I,  CgHgBr  was  used  and  the  use  of  AgCl 

omitted.  On  acidifying  with  HC1,  NaCl  would  precipitate.  No  def- 

As^Jii 

inite  arsenic  compound  which  corresponds  to  (Y  U2H5 
has  yet  been  isolated.  NH*CH2C00H 

It  was  also  attempted  to  introduce  a -C2H5  group  using 

AsCp}  As -oh 

^3  , and  then  using  the  supposedly  prepared  f)Nc  II 

NHo'HCl  Sju  5 

and  allowing  this  to  react  with  iNn2 

CICHgCOOH.  No  definite  results  however  were  obtained,  with  the 

exception  of  a product  which  did  not  possess  the  properties  of  the 

compound  in  view.  This  compound  has  as  yet  not  been  analyzed,  as 

no  suitable  solvent  for  purification  has  thus  far  been  found. 


-24- 

Due  to  so  many  possibilities  of  other  compounds  being  form- 
ed by  the  methods  so  far  used,  this  it  is  thought  may  explain  the 
inability  so  far  to  prepare  the  compound  readily. 

9.  Attempts  at  the  Preparation  of  Diphenyl-P-Diarsinic 
As^OH  ^sr8ll 


Acid. 


D 


N)ii 


At  present  experiments  are  in  progress  to  prepare  the  a- 
bove  named  compound. 

Three  methods  for  preparing  Diphenyl  Compounds  have  so  far 
been  tried. 

(1)  Cuprous  Chloride  Method. 


A o ^ 
ASsfjU 

Cl 

As?8„ 

U OH 
Cl 


The  same  proceedure  as  described  under  the  preparation  of 


A O *0 

As^OH 


was  used.  The  compound  expected  was 
but  analysis  of  the  compound  showed  it  to  be 


As?0H 


\ 


OH 


(2)  Ammoniacal  Cuprous  Oxide  Method. 

. A) 

As -.OH 

10  grams  of  rj  were  dissolved  in  100  cc  water  and 

. ml 

87  cc.  13 io  IIC1 , and 


IH2 


diazotized  with  75  cc.  N-NaNOg*  CugO  in 
NH^OH,  made  by  reducing  an  aqueous  solution  of  37  grams  CuSO^  in 
hhe  presence  of  NH^OH  until  a white  precipitate  of  CuNH^SOg  formed 
This  precipitate  was  dissolved  in  300  cc.  water  and  25  cc . NH^OH 
and  added  to  the  diazo  solution.  A yellowish  precipitated  formed 
which  resembles  Cu2C^  , but  has  as  yet  not  been  definitely  deter- 
mined . 


(3)  Copper  Powder  Method 


As 

,M)H 
OH 


Ov 

NH* 


in  40  grams  concentrated  H^SO^ 


31  grams  of 

and  150  grams  water  were  diazotized  with  23  grams 

KaN02*  Then  125  cc.  90^  C2H5OII  were  added  and  also  50  grams 


■ 


-25- 


copper  bronze.  A brown  colored  solution  resulted.  At  present 
work  is  confined  to  the  study  of  this  solution. 

IV . Summary . 

(1)  The  properties  of  P-Arsanilic  Acid  and  its  sodium  salt 
Atoxyl  is  described. 

(2)  The  structure  of  Atoxyl  is  discussed. 

(3)  The  preparation  and  properties  of  the  following  deriv- 
atives of  P-Arsanilic  Acid  are  given- 

1.  Phenylglycine-^-Arsinic  Acid. 

2.  Phenylglycine-P-Arsenious  Oxide. 

3.  Phenylglycine-P-Arsenious  Chloride. 

4.  P-Chlor-Arsenic  Acid. 

5.  P-Amino-Phenyl  Arsenious  Oxide. 

6.  P-Amino -Phenyl  Arsenious  Chloride. 

(4)  An  attempt  at  the  preparation  of  diphenyl-p-diarsonic 
acid  is  discussed. 

(5)  Attempts  at  the  preparation  of  phenylglycine-p-ethyl 
arsonic  acid  are  discussed. 


. 


- 


. 


. 

. 


* 


-26- 


BIBLIOGRAPHY. 

I.  Phenylstibinic  Acid. 

1.  Hasenbauraer , J.  -Ber.  31,  P, 2910-13. 

2.  Ilasenb'aumer , J.  -Ber.  31,  1398,  Pt.III,  P.  2913. 

3.  Michaelis  & Reese  -Annalen  233-234,  P.  43. 

4.  Morgan-Organic  Compounds  of  Arsenic  and  Antimony . -Intr . 

5.  Morgan-Ibid.  P.294. 

6.  Fried lander . D.R.P.  254,421  1912-12  P.  1084. 

7.  Pfeiffer.  -Ber.  37,  P.4620. 

8.  Morgan  and  Mickelthwar t . -Chem.  Soc.  Trans.  1911,  99,  P.2290. 

9.  Schmidt . -Annalen,  1920,  421,  P.174. 

II.  P-Arsanilic  Acid  and  its  Derivatives. 

1.  Ehrlich  and  Berthein.  -Ber.  43,  P.  917-19. 

2.  Bertheim. -Ber . 44,  P.  1070. 

3.  Bertheim. -Ber . 48,  P.  350. 

4.  Adler  and  Adler. -Ber.  41,  P.  932. 

5.  Benda  and  Kahn. -Ber.  41,  P.  1674. 

6.  Schmitz . -Ber . 47,  P.  363. 

7.  Bertheim  and  Ehrlich. -Ber . 40,  P.  3292. 

8.  Morgan. -Organic  Compounds  of  Arsenic  and  Antimony.  P.  158. 

9.  Ibid. -P.165. 

10.  Weyl. -P.843. 

11.  Benda. -Ber.  41,  P.2370. 

12.  Freidlander . - D.R.P.  204,664.  Vol.  IV  P.  1035. 

D.R.P.  206,057.  (1909). 

D.R.P.  254,187. 

13.  Vorlander  and  Meyer . -Annalen,  320,  P.  122p  P.  134. 

14.  Gatterman. -Ber . 23,  P.  1226. 

15.  Allman  and  Forgan.-Ber.  34,  P.  3802. 


■ 


